Epstein-Barr virus infection refers to a disease caused by Epstein-Barr virus (EBV), a human herpesvirus.

Infectious mononucleosis (IM)

Kissing disease

• Most EBV infections either are asymptomatic or cause a nonspecific viral illness.
• Incubation period is 1 to 2 mo, possibly followed by a prodrome of anorexia, low-grade fever, malaise, headache, and chills; after several days, clinical triad of pharyngitis, moderate to high fever, and adenopathy may appear, accompanied by fatigue and malaise.
• Pharyngitis is usually the most severe symptom; white or necrotic exudates are common.
• Symmetrical lymphadenopathy is most prominent in the posterior more than anterior cervical region but may be diffuse.
• Splenomegaly (50% of cases) is possible, most commonly during the second week of illness.
• Maculopapular or morbilliform rash is uncommon but will often occur in patients who receive ampicillin (Fig. E1). Patients may have palatal petechiae, periorbital, or palpebral edema. Mucocutaneous oral hairy leukoplakia (OHL), which is associated with intense EBV replication and the action of EBV-encoded proteins such as latent membrane protein-1, may occur.
• Possible IM presentation: Fever and adenopathy without pharyngitis.
• Nausea, vomiting, and anorexia are frequent in patients with IM, probably reflecting mild hepatitis encountered in 90% of infected individuals.
• Although complications such as spleen rupture, airway obstruction, and malignancy may be severe and fatal, they are uncommon and tend to resolve completely.
• Hematologic involvement includes hemolytic or aplastic anemia, thrombocytopenia, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, and disseminated intravascular coagulation (DIC). Pneumonia, myocarditis, pancreatitis, mesenteric adenitis, myositis, and glomerulonephritis may occur as well. Nervous system involvement includes Guillain-Barré syndrome, facial nerve palsy, meningoencephalitis, aseptic meningitis, transverse myelitis, peripheral neuritis, and optic neuritis.
• IM is usually a self-limited illness. Acute symptoms resolve in 1 to 2 wk, but symptoms of malaise and fatigue often persist for months.
• EBV is related to lymphoproliferative syndromes in transplant recipients and in AIDS patients.
• Increasing evidence showing an association between EBV infection and African Burkitt, B-cell or T-cell lymphoma, and nasopharyngeal carcinoma.

• EBV is a ubiquitous virus.
• Infection during childhood is much less likely to cause significant illness.
• Frequency of IM in late adolescence is attributed to the onset of social contact between the sexes.
• Close personal contact is usually necessary for transmission, although EBV is occasionally transmitted by blood transfusion; transfer via saliva while kissing may be responsible for many cases.

• Heterophile-negative IM caused by cytomegalovirus (CMV)
• Although clinical presentation similar, CMV more frequently follows transfusion
• Bacterial and viral causes of pharyngitis
• Toxoplasmosis
• Acute retroviral syndrome of HIV
• Lymphoma
• Lyme disease

Heterophile antibody and CBC with blood smear. Table E1 describes frequently determined EBV-specific antibodies.

• Increased WBC common, with a relative lymphocytosis of more than 50% and neutropenia identified.
• Hallmark of IM: Atypical lymphocytes of more than 10% (not pathognomonic) are found.
• Mild thrombocytopenia is present.
• Falling hematocrit signals the possibility of splenic rupture or immune hemolytic anemia.
• Elevated hepatocellular enzymes and cryoglobulins are found in most cases.
• Heterophile antibody:
  1. As measured by the monospot test, may be positive at presentation or may appear later in the course of illness. Its accuracy is 71% to 90% but has a 25% false-negative rate in the first week of illness.
  2. A negative test should be repeated in 1 wk if clinical suspicion is high.
  3. A false-positive test has been reported with primary HIV infection.
• Viral capsid antigen (VCA) IgG and IgM (Fig. E2) are rarely used for diagnosis but better value in children because heterophile antibody is negative in most children younger than 8 yr.
• PCR DNA for CMV is the test of choice in transplant recipients who develop lympho-proliferative syndromes.

Chest radiograph examination:

• May rarely show infiltrates
• Possible elevated left hemidiaphragm with splenic rupture

• Supportive including rest
• Splenectomy if rupture occurs
• Transfusions for severe anemia or thrombocytopenia

• Pharmacologic therapy is not indicated in uncomplicated illness.
• Avoid aspirin due to the risk of Reye syndrome.
• Avoid ampicillin and amoxicillin as their use can frequently precipitate a nonallergic rash. Azithromycin has also been implicated.
• Use of steroids is suggested in patients who have severe thrombocytopenia, hemolytic anemia, impending airway obstruction resulting from enlarged tonsils, or fulminant liver failure. Prednisone 60 to 80 mg PO qd for 3 days, then tapered over 1 to 2 wk.
• Although it may reduce initial viral shedding, there is little evidence to support the use of antiviral agents such as acyclovir in the management of IM.

An extremely rare, chronic form of IM with persistent fevers and fatigue has been described and should be differentiated from chronic fatigue syndrome, which is not related to EBV.

Eventual resolution of all symptoms

If more than mild illness

Avoidance of contact sports during the first month of illness because splenic rupture can occur even in the absence of clinically detectable splenomegaly in 0.1% to 0.5% of patients.

Epstein-Barr Virus Infection (Patient Information)

Mononucleosis (Related Key Topic)